The primary goal of this grant is to conduct structure-function studies to gain a better understanding of the regulation of transcriptional elongation by RNA Polymerase II (RNAP II). The phosphorylation state of the C- terminal domain (CTD) of RNAP II plays a key role in regulation of transcriptional elongation. FCP1, the first known CTD-specific phosphatase was recently cloned. In addition to its phosphatase activity, human FCP1 has been shown to directly interact with RAP74 (the large subunit of TFIIF), TFIIB and HIV-1 Tat, three factors which are known to affect the transcriptional elongation rates of RNAP II. The specific aims of this grant are to 1) determine a high-resolution NMR structure of the FCP1 binding domain of RAP74; 2) determine a high-resolution NMR structure of a complex between RAP74 and FCP1; 3) characterize the interaction between TFIIB and FCP1 using NMR spectroscopy; 4) conduct preliminary binding and NMR studies with FCPI, the Tat protein and the TAR RNA. This research will help us understand how regulation of FCP1 affects transcriptional elongation by RNAP II. In addition, our studies will provide new insights into how disruptions in the control of transcriptional regulation may occur in many forms of human cancer and viral infections.